Generic placeholder image

Current Drug Targets - Immune, Endocrine & Metabolic Disorders

Editor-in-Chief

ISSN (Print): 1568-0088
ISSN (Online): 1875-5917

Assessment of Modes of Action and Efficacy of Plasma Cholesterol- Lowering Drugs: Measurement of Cholesterol Absorption, Cholesterol Synthesis and Bile Acid Synthesis and Turnover Using Novel Stable Isotope Techniques

Author(s): Frans Stellaard and Folkert Kuipers

Volume 5, Issue 2, 2005

Page: [209 - 218] Pages: 10

DOI: 10.2174/1568005310505020209

Price: $65

Abstract

Several processes are involved in control of plasma cholesterol levels, e.g., intestinal cholesterol absorption, endogenous cholesterol synthesis and transport and bile acid synthesis. Adaptation of either of these processes allows the body to adapt to changes in dietary cholesterol intake. Disturbances herein may lead to hypercholesterolemia and increase the risk for atherosclerosis. Several approaches are available for plasma-cholesterol lowering therapies, particularly aimed at reduction of low-density lipoprotein (LDL) cholesterol. Currently used therapies aim to decrease (hepatic) cholesterol synthesis, to inhibit cholesterol absorption or to stimulate bile acid synthesis. The latter can be achieved by reducing bile acid absorption to alleviate the negative feedback control exerted by bile acids circulating in the body. Approaches to directly stimulate bile acid synthesis may become available. Novel drugs should be tested on the efficiency to influence their actual targets. Several techniques are available to measure cholesterol absorption, cholesterol synthesis and bile acid synthesis and absorption in vivo in human subjects. The most reliable techniques are based on the use of stable isotopes and mass spectrometry. This paper provides a condensed background on physiological parameters that determine cholesterol homeostasis, and potential new mechanisms of drug action and focuses, especially, on new techniques to monitor the effects of drugs in humans.

Keywords: low density lipoprotein (ldl), atp binding cassette (abc), hmg-coa


Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy